PLXDC2

Summary

PLXDC2 (plexin domain containing 2, HGNC:21013) is a protein-coding gene on chromosome 10p12.31, encoding Plexin domain-containing protein 2 (Q6UX71). May play a role in tumor angiogenesis.

Predicted to be located in membrane.

Source: NCBI Gene 84898 — RefSeq curated summary.

At a glance

• GWAS associations: 25
• Clinical variants (ClinVar): 93 total
• MANE Select transcript: NM_032812

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21013
Approved symbol	PLXDC2
Name	plexin domain containing 2
Location	10p12.31
Locus type	gene with protein product
Status	Approved
Aliases	TEM7R, FLJ14623, PLXDC2-OT
Ensembl gene	ENSG00000120594
Ensembl biotype	protein_coding
OMIM	606827
Entrez	84898

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 9 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000377238, ENST00000377242, ENST00000377252, ENST00000888732, ENST00000888733, ENST00000970498, ENST00000970499, ENST00000970500, ENST00000970501, ENST00000970502

RefSeq mRNA: 2 — MANE Select: NM_032812 NM_001282736, NM_032812

CCDS: CCDS60497, CCDS7132

Canonical transcript exons

ENST00000377252 — 14 exons

Exon	Start	End
ENSE00003230575	20001775	20001986
ENSE00003458751	20046869	20047015
ENSE00003481983	20217426	20217576
ENSE00003490345	20245345	20245505
ENSE00003517515	20176999	20177094
ENSE00003542374	20143295	20143417
ENSE00003551715	20219064	20219102
ENSE00003561627	20068170	20068239
ENSE00003567795	20164468	20164567
ENSE00003599318	20177328	20177409
ENSE00003610638	20147784	20147902
ENSE00003633266	20211669	20211729
ENSE00003707003	20279703	20289856
ENSE00003849803	19816432	19817191

Expression profiles

Bgee: expression breadth ubiquitous, 279 present calls, max score 99.04.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 22.2146 / max 484.9180, expressed in 1276 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
104165	12.5548	1145
104164	4.0033	927
104162	2.1597	742
104167	1.5073	666
104163	0.7442	356
104166	0.3869	236
104168	0.2994	137
104183	0.2293	101
104170	0.2101	85
104169	0.1194	60

Top tissues by expression

294 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	99.04	gold quality
tendon of biceps brachii	UBERON:0008188	98.25	gold quality
tendon	UBERON:0000043	97.80	gold quality
saphenous vein	UBERON:0007318	95.46	gold quality
synovial joint	UBERON:0002217	94.69	gold quality
adrenal tissue	UBERON:0018303	94.51	gold quality
skin of hip	UBERON:0001554	94.30	gold quality
monocyte	CL:0000576	94.28	gold quality
mononuclear cell	CL:0000842	94.03	gold quality
lower lobe of lung	UBERON:0008949	93.89	gold quality
leukocyte	CL:0000738	93.71	gold quality
descending thoracic aorta	UBERON:0002345	93.21	gold quality
mammary duct	UBERON:0001765	93.12	gold quality
hair follicle	UBERON:0002073	93.12	gold quality
buccal mucosa cell	CL:0002336	92.99	gold quality
nipple	UBERON:0002030	92.90	gold quality
thoracic aorta	UBERON:0001515	92.66	gold quality
ascending aorta	UBERON:0001496	92.62	gold quality
trigeminal ganglion	UBERON:0001675	92.60	gold quality
mammalian vulva	UBERON:0000997	92.53	gold quality
gall bladder	UBERON:0002110	92.46	gold quality
penis	UBERON:0000989	92.28	gold quality
right coronary artery	UBERON:0001625	91.97	gold quality
epithelium of mammary gland	UBERON:0003244	91.89	gold quality
medial globus pallidus	UBERON:0002477	91.84	gold quality
urethra	UBERON:0000057	91.74	gold quality
sural nerve	UBERON:0015488	91.68	gold quality
visceral pleura	UBERON:0002401	91.55	gold quality
aorta	UBERON:0000947	91.40	gold quality
pericardium	UBERON:0002407	91.28	gold quality

Single-cell (SCXA)

Detected in 15 experiment(s), a significant marker in 14.

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	8058.49
E-HCAD-30	yes	7814.95
E-GEOD-180759	yes	7285.19
E-HCAD-25	yes	5165.16
E-ANND-2	yes	4448.61
E-MTAB-6678	yes	43.78
E-GEOD-84465	yes	39.78
E-CURD-112	yes	32.29
E-MTAB-9221	yes	26.01
E-HCAD-6	yes	18.63
E-MTAB-10287	yes	16.21
E-MTAB-9067	yes	13.13
E-MTAB-9801	yes	6.22
E-MTAB-11268	no	2959.25
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

385 targeting PLXDC2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-432-3P	100.00	67.86	705
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-371A-3P	99.99	66.77	91
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-4775	99.98	75.00	6394

Literature-anchored findings (GeneRIF, showing 10)

• We identified a genetic association for susceptibility to retinopathy in 5 novel chromosomal regions and PLXDC2 and ARHGAP22, the latter 2 of which are genes implicated in endothelial cell angiogenesis and increased capillary permeability. (PMID:21310492)
• PLXDC1 and PLXDC2 as the transmembrane receptors for the multifunctional factor PEDF. (PMID:25535841)
• The genetic variant near the PLXDC2 gene was found to influence the risk of POAG by increasing IOP in the Japanese population. (PMID:28930887)
• PLXDC2 rs7081455 is not associated with primary open angle glaucoma or its clinical phenotypes in patients of Saudi origin. (PMID:30326957)
• A Genome Wide Association Study on plasma FV levels identified PLXDC2 as a new modifier of the coagulation process. (PMID:31271701)
• Expression Pattern of Plexin Domain Containing 2 in Human Hepatocellular Carcinoma. (PMID:32202949)
• Plxdc family members are novel receptors for the rhesus monkey rhadinovirus (RRV). (PMID:33657166)
• Plexin domain containing protein 2 is more expressed within the invasive area of human colorectal cancer tissues. (PMID:34146255)
• The Upregulation of PLXDC2 Correlates with Immune Microenvironment Characteristics and Predicts Prognosis in Gastric Cancer. (PMID:34777633)
• Adaptive c-Met-PLXDC2 Signaling Axis Mediates Cancer Stem Cell Plasticity to Confer Radioresistance-associated Aggressiveness in Head and Neck Cancer. (PMID:37089864)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	plxdc2b	ENSDARG00000059950
danio_rerio	plxdc2a	ENSDARG00000077219
mus_musculus	Plxdc2	ENSMUSG00000026748
rattus_norvegicus	Plxdc2	ENSRNOG00000000142
drosophila_melanogaster	l(1)G0289	FBGN0028331
caenorhabditis_elegans		WBGENE00007982

Paralogs (1): PLXDC1 (ENSG00000161381)

Protein

Protein identifiers

Plexin domain-containing protein 2 — Q6UX71 (reviewed: Q6UX71)

Alternative names: Tumor endothelial marker 7-related protein

All UniProt accessions (1): Q6UX71

UniProt curated annotations — full annotation on UniProt →

Function. May play a role in tumor angiogenesis.

Subunit / interactions. Interacts with CTTN.

Subcellular location. Membrane.

Tissue specificity. Expressed in the endothelial cells of the stroma but not in the endothelial cells of normal colonic tissue.

Similarity. Belongs to the plexin family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q6UX71-1	1	yes
Q6UX71-2	2
Q6UX71-3	3

RefSeq proteins (2): NP_001269665, NP_116201* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002165	Plexin_repeat	Repeat
IPR016201	PSI	Domain
IPR031152	PLXDC	Family

Pfam: PF01437

UniProt features (14 total): splice variant 2, sequence variant 2, topological domain 2, glycosylation site 2, signal peptide 1, chain 1, transmembrane region 1, domain 1, region of interest 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6UX71-F1	69.80	0.40

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 506

Glycosylation sites (2): 103, 160

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 304 (showing top): FOXO1_01, NFKB_Q6, ZIC1_01, COATES_MACROPHAGE_M1_VS_M2_UP, AACTTT_UNKNOWN, ELK1_01, VDR_Q3, CUI_TCF21_TARGETS_2_DN, CERVERA_SDHB_TARGETS_1_UP, CTGYNNCTYTAA_UNKNOWN, MODULE_48, CCCNNGGGAR_OLF1_01, MODULE_95, RIGGI_EWING_SARCOMA_PROGENITOR_UP, IVANOVA_HEMATOPOIESIS_STEM_CELL_LONG_TERM

GO Biological Process (0):

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (1): membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

876 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PLXDC2	HCLS1	P14317	768
PLXDC2	CTTN	Q14247	766
PLXDC2	SERPINF1	P36955	607
PLXDC2	ZP4	Q12836	540
PLXDC2	TMTC2	Q8N394	480
PLXDC2	RBM6	P78332	478
PLXDC2	ARHGAP22	Q7Z5H3	441
PLXDC2	KLHL25	Q9H0H3	431
PLXDC2	KIAA1217	Q5T5P2	409
PLXDC2	SIRT7	Q9NRC8	406
PLXDC2	NREP	Q16612	400
PLXDC2	ATP11A	P98196	399
PLXDC2	DIRAS1	O95057	395
PLXDC2	CGRRF1	Q99675	386
PLXDC2	ADGRD1	Q6QNK2	386

IntAct

78 interactions, top by confidence:

A	B	Type	Score
COPRS	PRMT5	psi-mi:“MI:0914”(association)	0.770
SLC1A1	AGPAT2	psi-mi:“MI:0914”(association)	0.640
UBE2K	ZFTRAF1	psi-mi:“MI:0914”(association)	0.620
AKR1C4	PLXDC2	psi-mi:“MI:0915”(physical association)	0.590
PLXDC2	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
IGFBP1	SUSD5	psi-mi:“MI:0914”(association)	0.530
RHEX	NOS1AP	psi-mi:“MI:0914”(association)	0.530
SERPINB8	TOX4	psi-mi:“MI:0914”(association)	0.530
HACL1	PLXDC2	psi-mi:“MI:0914”(association)	0.530
PICK1	ILVBL	psi-mi:“MI:0914”(association)	0.530
INSL5	COCH	psi-mi:“MI:0914”(association)	0.530
AKR1D1	AKR1B10	psi-mi:“MI:0914”(association)	0.530
NRBP1	TBC1D4	psi-mi:“MI:0914”(association)	0.530
UBR2	PAM	psi-mi:“MI:0914”(association)	0.530
TRAT1	ACADVL	psi-mi:“MI:0914”(association)	0.530
LRRC42	CUL3	psi-mi:“MI:0914”(association)	0.530
BOD1	PLXDC2	psi-mi:“MI:0914”(association)	0.530
SFXN5	TOMM40	psi-mi:“MI:0914”(association)	0.530
CDH8	ARVCF	psi-mi:“MI:0914”(association)	0.530
DOK4	KDM1A	psi-mi:“MI:0914”(association)	0.530
LDLRAD1	ADAM10	psi-mi:“MI:0914”(association)	0.530

BioGRID (100): PLXDC2 (Affinity Capture-MS), PLXDC2 (Affinity Capture-MS), PLXDC2 (Affinity Capture-MS), PLXDC2 (Affinity Capture-MS), PLXDC2 (Affinity Capture-MS), PLXDC2 (Affinity Capture-MS), PLXDC2 (Affinity Capture-MS), PLXDC2 (Affinity Capture-MS), PLXDC2 (Affinity Capture-MS), PLXDC2 (Biochemical Activity), TMEM199 (Affinity Capture-MS), CCDC115 (Affinity Capture-MS), PLXDC2 (Affinity Capture-MS), PLXDC2 (Affinity Capture-MS), PLXDC2 (Affinity Capture-MS)

ESM2 similar proteins: A0A0D3QS97, A1L314, D3YXF5, E7F0Z8, O75339, P02748, P06682, P06683, P07357, P07358, P10643, P10820, P35763, P48747, P48770, P51578, P55314, P79755, P98136, P98137, Q2KJC3, Q2M385, Q3MHN2, Q3V5L5, Q5RBP9, Q62930, Q64663, Q66K08, Q66S13, Q66S17, Q66S21, Q66S25, Q6UX71, Q765H6, Q8BG22, Q8BH35, Q8K182, Q8L612, Q8N2E2, Q90X85

Diamond homologs: Q6DE92, Q6UX71, Q8IUK5, Q91ZV7, Q9DC11

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

93 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	71
Likely benign	6
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

3648 predictions. Top by Δscore:

Variant	Effect	Δscore
10:19817192:G:C	donor_loss	1.0000
10:19817192:G:GG	donor_gain	1.0000
10:19817193:T:A	donor_loss	1.0000
10:20001769:A:AG	acceptor_gain	1.0000
10:20001770:A:G	acceptor_gain	1.0000
10:20001772:CAGAT:C	acceptor_loss	1.0000
10:20001773:A:AG	acceptor_gain	1.0000
10:20001773:AGATT:A	acceptor_gain	1.0000
10:20001774:G:GA	acceptor_gain	1.0000
10:20001774:GA:G	acceptor_gain	1.0000
10:20001774:GAT:G	acceptor_gain	1.0000
10:20001774:GATT:G	acceptor_gain	1.0000
10:20001774:GATTG:G	acceptor_gain	1.0000
10:20001982:TCGAG:T	donor_loss	1.0000
10:20001983:CGAGG:C	donor_loss	1.0000
10:20001986:GGT:G	donor_loss	1.0000
10:20001987:GTAG:G	donor_loss	1.0000
10:20046863:TTGCA:T	acceptor_loss	1.0000
10:20046864:TGCAG:T	acceptor_loss	1.0000
10:20046866:CA:C	acceptor_loss	1.0000
10:20046867:A:AG	acceptor_gain	1.0000
10:20046867:A:T	acceptor_loss	1.0000
10:20046867:AGGAG:A	acceptor_gain	1.0000
10:20046868:G:GG	acceptor_gain	1.0000
10:20046868:GGAGG:G	acceptor_gain	1.0000
10:20047011:CTGCA:C	donor_gain	1.0000
10:20047012:TGCA:T	donor_gain	1.0000
10:20047013:GCA:G	donor_gain	1.0000
10:20047013:GCAG:G	donor_gain	1.0000
10:20047013:GCAGT:G	donor_loss	1.0000

AlphaMissense

3487 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:20046990:T:C	L149S	1.000
10:20046990:T:G	L149W	1.000
10:20046993:C:T	S150F	1.000
10:20047001:C:G	H153D	1.000
10:20047005:G:C	R154P	1.000
10:20047010:G:C	A156P	1.000
10:20047011:C:A	A156D	1.000
10:20047013:G:C	A157P	1.000
10:20068204:G:T	G169V	1.000
10:20068234:C:T	T179I	1.000
10:20068236:G:A	G180R	1.000
10:20068236:G:C	G180R	1.000
10:20068236:G:T	G180W	1.000
10:20068237:G:A	G180E	1.000
10:20068239:G:C	G181R	1.000
10:20068239:G:T	G181C	1.000
10:20143295:G:A	G181D	1.000
10:20143295:G:T	G181V	1.000
10:20143297:T:C	F182L	1.000
10:20143298:T:C	F182S	1.000
10:20143298:T:G	F182C	1.000
10:20143299:C:A	F182L	1.000
10:20143299:C:G	F182L	1.000
10:20143301:T:A	I183K	1.000
10:20143309:G:A	G186R	1.000
10:20143309:G:C	G186R	1.000
10:20143310:G:T	G186V	1.000
10:20143331:T:A	L193Q	1.000
10:20143331:T:C	L193P	1.000
10:20143349:T:A	I199K	1.000

dbSNP variants (sampled 300 via entrez): RS1000008325 (10:19892984 A>G), RS1000012659 (10:20065089 T>A), RS1000013598 (10:19974008 G>A,T), RS1000022396 (10:20144054 T>G), RS1000026584 (10:19992237 G>A,T), RS1000028202 (10:19930006 G>C), RS1000030475 (10:20064837 C>T), RS1000043281 (10:20218115 T>A,G), RS1000051173 (10:20156677 G>A), RS1000057021 (10:20236730 T>A), RS1000058413 (10:20187147 G>A), RS1000075692 (10:20217806 T>A,G), RS1000079956 (10:19891877 A>G), RS1000081881 (10:19929653 C>T), RS1000083066 (10:20054378 A>C)

Disease associations

OMIM: gene MIM:606827 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

25 associations (top):

Study	Trait	p-value
GCST000966_2	Diabetic retinopathy	3.000000e-07
GCST002104_13	Bronchopulmonary dysplasia	3.000000e-06
GCST003141_9	Proteinuria and chronic kidney disease	1.000000e-06
GCST003479_4	Hair color	5.000000e-06
GCST003654_15	Bone mineral density (Ward’s triangle area)	7.000000e-07
GCST003992_45	Photic sneeze reflex	6.000000e-13
GCST006017_4	Prothrombin time	4.000000e-19
GCST006018_2	Activated partial thromboplastin time	3.000000e-09
GCST006288_462	Heel bone mineral density	5.000000e-08
GCST006288_466	Heel bone mineral density	4.000000e-09
GCST006288_487	Heel bone mineral density	9.000000e-06
GCST006288_626	Heel bone mineral density	1.000000e-12
GCST006288_627	Heel bone mineral density	5.000000e-12
GCST006585_2485	Blood protein levels	4.000000e-07
GCST006631_34	Nicotine dependence and major depression (severity of comorbidity)	4.000000e-06
GCST006979_561	Heel bone mineral density	7.000000e-31
GCST006979_562	Heel bone mineral density	1.000000e-27
GCST007096_10	Pulse pressure	1.000000e-08
GCST007269_183	Pulse pressure	7.000000e-09
GCST008461_1	Plasma factor V levels in venous thrombosis	8.000000e-15
GCST008462_8	Plasma factor V levels in venous thrombosis (conditioned on rs6027)	3.000000e-07
GCST009091_6	Abdominal aortic calcification levels	8.000000e-07
GCST009959_17	Retinal detachment or retinal break	4.000000e-06
GCST011691_7	Total cholesterol levels	5.000000e-07
GCST011694_5	Non-HDL cholesterol levels	4.000000e-07

EFO canonical traits (11, from GWAS)

EFO ID	Trait name
EFO:0007785	femoral neck bone mineral density
EFO:0007887	autosomal dominant compelling helio-ophthalmic outburst syndrome
EFO:0008390	prothrombin time measurement
EFO:0009270	heel bone mineral density
EFO:0007006	depressive symptom measurement
EFO:0009262	nicotine dependence symptom count
EFO:0005763	pulse pressure measurement
EFO:0010272	abdominal aortic calcification measurement
EFO:0010698	retinal break
EFO:0004574	total cholesterol measurement
EFO:0005689	non-high density lipoprotein cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

54 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, decreases methylation	4
trichostatin A	affects cotreatment, decreases expression	3
bisphenol A	affects methylation, increases expression	2
Resveratrol	increases expression, increases phosphorylation	2
Air Pollutants	decreases expression, increases abundance	2
Smoke	decreases expression, increases abundance	2
Tobacco Smoke Pollution	affects expression, decreases expression	2
Cyclosporine	decreases expression	2
Cadmium Chloride	decreases expression, increases abundance	2
aristolochic acid I	decreases expression	1
GSK-J4	decreases expression	1
sodium arsenate	increases abundance, decreases expression	1
terbufos	increases methylation	1
arsenite	decreases expression	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
sulforaphane	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	decreases expression	1
zinc chromate	increases abundance, increases expression	1
aflatoxin B2	decreases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	increases abundance, increases expression	1
azoxystrobin	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
incobotulinumtoxinA	increases expression	1
picoxystrobin	decreases expression	1
Dasatinib	increases expression	1
Acetaminophen	increases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.